AU2020357816A1 - Modulation of microbiota compositions using targeted nucleases - Google Patents
Modulation of microbiota compositions using targeted nucleases Download PDFInfo
- Publication number
- AU2020357816A1 AU2020357816A1 AU2020357816A AU2020357816A AU2020357816A1 AU 2020357816 A1 AU2020357816 A1 AU 2020357816A1 AU 2020357816 A AU2020357816 A AU 2020357816A AU 2020357816 A AU2020357816 A AU 2020357816A AU 2020357816 A1 AU2020357816 A1 AU 2020357816A1
- Authority
- AU
- Australia
- Prior art keywords
- crispr
- nucleic acid
- nuclease
- sequence
- chromosome
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 101710163270 Nuclease Proteins 0.000 title claims abstract description 112
- 239000000203 mixture Substances 0.000 title abstract description 19
- 241000736262 Microbiota Species 0.000 title description 11
- 241000894006 Bacteria Species 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 35
- 108020005004 Guide RNA Proteins 0.000 claims description 96
- 108091033409 CRISPR Proteins 0.000 claims description 56
- 230000001939 inductive effect Effects 0.000 claims description 56
- 241000606125 Bacteroides Species 0.000 claims description 53
- 238000010354 CRISPR gene editing Methods 0.000 claims description 52
- 210000000349 chromosome Anatomy 0.000 claims description 49
- 239000013598 vector Substances 0.000 claims description 34
- 150000007523 nucleic acids Chemical class 0.000 claims description 29
- 241000606123 Bacteroides thetaiotaomicron Species 0.000 claims description 27
- 241000282414 Homo sapiens Species 0.000 claims description 24
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 23
- 102000039446 nucleic acids Human genes 0.000 claims description 23
- 108020004707 nucleic acids Proteins 0.000 claims description 23
- 230000012010 growth Effects 0.000 claims description 22
- 230000014509 gene expression Effects 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 16
- 229930101283 tetracycline Natural products 0.000 claims description 16
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 claims description 16
- 230000001580 bacterial effect Effects 0.000 claims description 14
- 241000606124 Bacteroides fragilis Species 0.000 claims description 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 12
- 241000894007 species Species 0.000 claims description 12
- 241000606215 Bacteroides vulgatus Species 0.000 claims description 9
- 102000052510 DNA-Binding Proteins Human genes 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 241001032450 Bacteroides cellulosilyticus Species 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- 241001135228 Bacteroides ovatus Species 0.000 claims description 6
- 101710096438 DNA-binding protein Proteins 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 241001109645 Bacteroides helcogenes Species 0.000 claims description 5
- 241000168636 Bacteroides salanitronis Species 0.000 claims description 5
- 241000606219 Bacteroides uniformis Species 0.000 claims description 5
- 241000115153 Bacteroides xylanisolvens Species 0.000 claims description 5
- 238000009169 immunotherapy Methods 0.000 claims description 5
- 210000003578 bacterial chromosome Anatomy 0.000 claims description 4
- 238000004113 cell culture Methods 0.000 claims description 4
- 230000008030 elimination Effects 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 210000002902 archaeal chromosome Anatomy 0.000 claims 1
- 239000013611 chromosomal DNA Substances 0.000 abstract description 9
- 238000007634 remodeling Methods 0.000 abstract description 2
- 239000013612 plasmid Substances 0.000 description 58
- 125000003729 nucleotide group Chemical group 0.000 description 52
- 230000008685 targeting Effects 0.000 description 50
- 239000002773 nucleotide Substances 0.000 description 48
- 230000010354 integration Effects 0.000 description 38
- 108090000623 proteins and genes Proteins 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 27
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 24
- 239000002609 medium Substances 0.000 description 23
- 108020004414 DNA Proteins 0.000 description 22
- 108091079001 CRISPR RNA Proteins 0.000 description 19
- 239000006161 blood agar Substances 0.000 description 18
- 244000005709 gut microbiome Species 0.000 description 17
- 230000002147 killing effect Effects 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 230000021615 conjugation Effects 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- 102000018120 Recombinases Human genes 0.000 description 14
- 108010091086 Recombinases Proteins 0.000 description 14
- 230000027455 binding Effects 0.000 description 14
- 108010061833 Integrases Proteins 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 230000001105 regulatory effect Effects 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 102100034343 Integrase Human genes 0.000 description 12
- 238000010790 dilution Methods 0.000 description 12
- 239000012895 dilution Substances 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229960003276 erythromycin Drugs 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 101100445525 Lysinibacillus sphaericus ermG gene Proteins 0.000 description 9
- 241001515720 Bacteroides cellulosilyticus WH2 Species 0.000 description 8
- 239000000835 fiber Substances 0.000 description 8
- 108091026890 Coding region Proteins 0.000 description 7
- 238000001712 DNA sequencing Methods 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 230000003115 biocidal effect Effects 0.000 description 7
- 230000002759 chromosomal effect Effects 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 230000006798 recombination Effects 0.000 description 7
- 238000005215 recombination Methods 0.000 description 7
- 230000010076 replication Effects 0.000 description 7
- 125000002652 ribonucleotide group Chemical group 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 6
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 6
- 101000910035 Streptococcus pyogenes serotype M1 CRISPR-associated endonuclease Cas9/Csn1 Proteins 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 230000002550 fecal effect Effects 0.000 description 6
- 238000003304 gavage Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 230000000813 microbial effect Effects 0.000 description 6
- 108091093088 Amplicon Proteins 0.000 description 5
- 101100478982 Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / JCM 5827 / CCUG 10774 / NCTC 10582 / VPI-5482 / E50) susC gene Proteins 0.000 description 5
- 241000304137 Bacteroides thetaiotaomicron VPI-5482 Species 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 108091092724 Noncoding DNA Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108020004465 16S ribosomal RNA Proteins 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108091028664 Ribonucleotide Proteins 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical compound N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 description 4
- 229960002682 cefoxitin Drugs 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 239000005547 deoxyribonucleotide Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000005782 double-strand break Effects 0.000 description 4
- 239000003651 drinking water Substances 0.000 description 4
- 235000020188 drinking water Nutrition 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000006041 probiotic Substances 0.000 description 4
- 235000018291 probiotics Nutrition 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000002336 ribonucleotide Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 101150090898 tdk gene Proteins 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 101001123982 Arabidopsis thaliana Protochlorophyllide reductase C, chloroplastic Proteins 0.000 description 3
- 241000217846 Bacteroides caccae Species 0.000 description 3
- 241001221145 Bacteroides pyogenes Species 0.000 description 3
- 208000037088 Chromosome Breakage Diseases 0.000 description 3
- 238000007702 DNA assembly Methods 0.000 description 3
- 230000007018 DNA scission Effects 0.000 description 3
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 3
- 241000078280 Escherichia coli S17 Species 0.000 description 3
- 101710116435 Outer membrane protein Proteins 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 101710130181 Protochlorophyllide reductase A, chloroplastic Proteins 0.000 description 3
- 101710138718 Protochlorophyllide reductase B, chloroplastic Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 241000193996 Streptococcus pyogenes Species 0.000 description 3
- 241000320123 Streptococcus pyogenes M1 GAS Species 0.000 description 3
- 108091028113 Trans-activating crRNA Proteins 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000002619 cancer immunotherapy Methods 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000012405 in silico analysis Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 210000003705 ribosome Anatomy 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 101150011187 susC gene Proteins 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 241000203069 Archaea Species 0.000 description 2
- 241000402140 Bacteroides finegoldii Species 0.000 description 2
- 241001195773 Bacteroides massiliensis Species 0.000 description 2
- 241000073659 Bacteroides vulgatus ATCC 8482 Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 241001135232 Odoribacter splanchnicus Species 0.000 description 2
- 241000606210 Parabacteroides distasonis Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000589952 Planctomyces Species 0.000 description 2
- 229930185560 Pseudouridine Natural products 0.000 description 2
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 2
- 101710090029 Replication-associated protein A Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 101150024470 cfxA gene Proteins 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000012321 colectomy Methods 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 230000000529 probiotic effect Effects 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 241001478277 uncultured delta proteobacterium Species 0.000 description 2
- SPFAOPCHYIJPHJ-WPJNXPDPSA-N (4s,4as,12ar)-4-(dimethylamino)-1,10,11,12a-tetrahydroxy-6-methyl-3,12-dioxo-4a,5-dihydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(O)=C2C(O)=C(C(=O)[C@@]3(O)[C@H]([C@@H](C(C(C(N)=O)=C3O)=O)N(C)C)C3)C3=C(C)C2=C1 SPFAOPCHYIJPHJ-WPJNXPDPSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 241000007909 Acaryochloris Species 0.000 description 1
- 241001135190 Acetohalobium Species 0.000 description 1
- 241000604451 Acidaminococcus Species 0.000 description 1
- 241000093740 Acidaminococcus sp. Species 0.000 description 1
- 241000266272 Acidithiobacillus Species 0.000 description 1
- 241001134629 Acidothermus Species 0.000 description 1
- 241000116863 Agrobacterium radiobacter DSM 30147 Species 0.000 description 1
- 241000702460 Akkermansia Species 0.000 description 1
- 241001147780 Alicyclobacillus Species 0.000 description 1
- 241001063273 Alicyclobacillus acidiphilus Species 0.000 description 1
- 241001135230 Alistipes putredinis Species 0.000 description 1
- 241001655243 Allochromatium Species 0.000 description 1
- 241000147157 Ammonifex Species 0.000 description 1
- 241000192542 Anabaena Species 0.000 description 1
- 101100412103 Arabidopsis thaliana REC3 gene Proteins 0.000 description 1
- 241001495180 Arthrospira Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 101100301559 Bacillus anthracis repS gene Proteins 0.000 description 1
- 241001037822 Bacillus bacterium Species 0.000 description 1
- 241000193749 Bacillus coagulans Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241001674039 Bacteroides acidifaciens Species 0.000 description 1
- 241000168635 Bacteroides barnesiae Species 0.000 description 1
- 241000859775 Bacteroides caecicola Species 0.000 description 1
- 241000685477 Bacteroides caecigallinarum Species 0.000 description 1
- 241000801600 Bacteroides clarus Species 0.000 description 1
- 241001220439 Bacteroides coprocola Species 0.000 description 1
- 241000545821 Bacteroides coprophilus Species 0.000 description 1
- 241001631983 Bacteroides coprosuis Species 0.000 description 1
- 241001105998 Bacteroides dorei Species 0.000 description 1
- 241001135322 Bacteroides eggerthii Species 0.000 description 1
- 241000337516 Bacteroides faecichinchillae Species 0.000 description 1
- 241000956551 Bacteroides faecis Species 0.000 description 1
- 241000801629 Bacteroides fluxus Species 0.000 description 1
- 241000514947 Bacteroides galacturonicus Species 0.000 description 1
- 241000859740 Bacteroides gallinaceum Species 0.000 description 1
- 241000168642 Bacteroides gallinarum Species 0.000 description 1
- 241001567982 Bacteroides graminisolvens Species 0.000 description 1
- 241001135237 Bacteroides heparinolyticus Species 0.000 description 1
- 241000047484 Bacteroides intestinalis Species 0.000 description 1
- 241000947128 Bacteroides luti Species 0.000 description 1
- 241000514665 Bacteroides neonati Species 0.000 description 1
- 241001122266 Bacteroides nordii Species 0.000 description 1
- 241000801630 Bacteroides oleiciplenus Species 0.000 description 1
- 241000962950 Bacteroides ovatus ATCC 8483 Species 0.000 description 1
- 241000828416 Bacteroides paurosaccharolyticus Species 0.000 description 1
- 241001220441 Bacteroides plebeius Species 0.000 description 1
- 241000859824 Bacteroides propionicifaciens Species 0.000 description 1
- 241000660102 Bacteroides reticulotermitis Species 0.000 description 1
- 241001652281 Bacteroides rodentium Species 0.000 description 1
- 241001122267 Bacteroides salyersiae Species 0.000 description 1
- 241000911892 Bacteroides sartorii Species 0.000 description 1
- 241000337504 Bacteroides stercorirosoris Species 0.000 description 1
- 241000204294 Bacteroides stercoris Species 0.000 description 1
- 241001234061 Bacteroides timonensis Species 0.000 description 1
- 241000514942 Bacteroides xylanolyticus Species 0.000 description 1
- 241001135233 Bacteroides zoogleoformans Species 0.000 description 1
- 241000268242 Barnesiella sp. Species 0.000 description 1
- 241000927510 Barnesiella viscericola Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 241001453642 Borrelia johnsonii Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241001600148 Burkholderiales Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000606208 Campylobacter gracilis Species 0.000 description 1
- 241000589875 Campylobacter jejuni Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108700004991 Cas12a Proteins 0.000 description 1
- 102100031437 Cell cycle checkpoint protein RAD1 Human genes 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 101100247969 Clostridium saccharobutylicum regA gene Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 241001262170 Collinsella aerofaciens Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000065719 Crocosphaera Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 241000159506 Cyanothece Species 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 102100033934 DNA repair protein RAD51 homolog 2 Human genes 0.000 description 1
- 101710141836 DNA-binding protein HU homolog Proteins 0.000 description 1
- 206010069150 Discordant twin Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 101100412434 Escherichia coli (strain K12) repB gene Proteins 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241001468125 Exiguobacterium Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241001617393 Finegoldia Species 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 108700036482 Francisella novicida Cas9 Proteins 0.000 description 1
- 241000589599 Francisella tularensis subsp. novicida Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 101001130384 Homo sapiens Cell cycle checkpoint protein RAD1 Proteins 0.000 description 1
- 101001132307 Homo sapiens DNA repair protein RAD51 homolog 2 Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102000012330 Integrases Human genes 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241001430082 Ktedonobacter Species 0.000 description 1
- 241001112693 Lachnospiraceae Species 0.000 description 1
- 241000689670 Lachnospiraceae bacterium ND2006 Species 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001453171 Leptotrichia Species 0.000 description 1
- 241000029603 Leptotrichia shahii Species 0.000 description 1
- 241000029590 Leptotrichia wadei Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241001134698 Lyngbya Species 0.000 description 1
- 241000206589 Marinobacter Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241000204639 Methanohalobium Species 0.000 description 1
- 241000179980 Microcoleus Species 0.000 description 1
- 241000192701 Microcystis Species 0.000 description 1
- 241000190905 Microscilla Species 0.000 description 1
- 101710174628 Modulating protein YmoA Proteins 0.000 description 1
- 241000588772 Morganella morganii Species 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- VQAYFKKCNSOZKM-IOSLPCCCSA-N N(6)-methyladenosine Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VQAYFKKCNSOZKM-IOSLPCCCSA-N 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- VQAYFKKCNSOZKM-UHFFFAOYSA-N NSC 29409 Natural products C1=NC=2C(NC)=NC=NC=2N1C1OC(CO)C(O)C1O VQAYFKKCNSOZKM-UHFFFAOYSA-N 0.000 description 1
- 241000167284 Natranaerobius Species 0.000 description 1
- 241000588654 Neisseria cinerea Species 0.000 description 1
- 241000135938 Nitratifractor Species 0.000 description 1
- 241000192147 Nitrosococcus Species 0.000 description 1
- 241000203622 Nocardiopsis Species 0.000 description 1
- 241000059630 Nodularia <Cyanobacteria> Species 0.000 description 1
- 241000192656 Nostoc Species 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000202223 Oenococcus Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000192497 Oscillatoria Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000905671 Paludibacter sp. Species 0.000 description 1
- 241000030714 Parabacteroides goldsteinii Species 0.000 description 1
- 241001472606 Parabacteroides sp. Species 0.000 description 1
- 241001267951 Parasutterella Species 0.000 description 1
- 241001425545 Pelotomaculum Species 0.000 description 1
- 241001135648 Petrotoga Species 0.000 description 1
- 241000512220 Polaromonas Species 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- 241000183024 Populus tremula Species 0.000 description 1
- 241000711943 Porphyromonadaceae bacterium Species 0.000 description 1
- 241000605861 Prevotella Species 0.000 description 1
- 241001135223 Prevotella melaninogenica Species 0.000 description 1
- 241001135262 Prevotella oris Species 0.000 description 1
- 241000611831 Prevotella sp. Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000519590 Pseudoalteromonas Species 0.000 description 1
- 241001495182 Pseudobacteroides cellulosolvens Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000232299 Ralstonia Species 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 241000095588 Ruminococcaceae Species 0.000 description 1
- 241000192031 Ruminococcus Species 0.000 description 1
- 241000192026 Ruminococcus flavefaciens Species 0.000 description 1
- 101100528972 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RPD3 gene Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000094100 Schleiferia Species 0.000 description 1
- 108091027568 Single-stranded nucleotide Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 101100166144 Staphylococcus aureus cas9 gene Proteins 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 101100114425 Streptococcus agalactiae copG gene Proteins 0.000 description 1
- 241001501869 Streptococcus pasteurianus Species 0.000 description 1
- 101100166147 Streptococcus thermophilus cas9 gene Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000702031 Streptomyces phage R4 Species 0.000 description 1
- 241000701955 Streptomyces virus phiC31 Species 0.000 description 1
- 241000203590 Streptosporangium Species 0.000 description 1
- 241001580973 Subdoligranulum variabile Species 0.000 description 1
- 241000192707 Synechococcus Species 0.000 description 1
- 241000204315 Thermosipho <sea snail> Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 241001261005 Verrucomicrobia Species 0.000 description 1
- 241000605941 Wolinella Species 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009604 anaerobic growth Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000013602 bacteriophage vector Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 238000004173 biogeochemical cycle Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000029602 competition with other organism Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000007784 diverticulitis Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 230000000688 enterotoxigenic effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229920002457 flexible plastic Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 235000006486 human diet Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000020802 micronutrient deficiency Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000009343 monoculture Methods 0.000 description 1
- 229940076266 morganella morganii Drugs 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- MUDHHWLZEUJOQU-UHFFFAOYSA-N n-(3-ethoxypropyl)-1-phenylcyclohexan-1-amine Chemical compound C=1C=CC=CC=1C1(NCCCOCC)CCCCC1 MUDHHWLZEUJOQU-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- -1 phosphoryl groups Chemical group 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 101150044854 repA gene Proteins 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229940063638 ridaura Drugs 0.000 description 1
- 230000001523 saccharolytic effect Effects 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 101150024821 tetO gene Proteins 0.000 description 1
- 101150061166 tetR gene Proteins 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000009424 underpinning Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/101—Plasmid DNA for bacteria
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/002—Vectors comprising a special translation-regulating system controllable or inducible
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962908130P | 2019-09-30 | 2019-09-30 | |
| US62/908,130 | 2019-09-30 | ||
| US201962909078P | 2019-10-01 | 2019-10-01 | |
| US62/909,078 | 2019-10-01 | ||
| US202063052825P | 2020-07-16 | 2020-07-16 | |
| US63/052,825 | 2020-07-16 | ||
| PCT/US2020/053304 WO2021067291A1 (en) | 2019-09-30 | 2020-09-29 | Modulation of microbiota compositions using targeted nucleases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2020357816A1 true AU2020357816A1 (en) | 2022-04-14 |
Family
ID=72896108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2020357816A Abandoned AU2020357816A1 (en) | 2019-09-30 | 2020-09-29 | Modulation of microbiota compositions using targeted nucleases |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20210095273A1 (https=) |
| EP (1) | EP4038185A1 (https=) |
| JP (2) | JP2022549519A (https=) |
| KR (1) | KR20220051259A (https=) |
| CN (1) | CN114929873A (https=) |
| AU (1) | AU2020357816A1 (https=) |
| BR (1) | BR112022005831A2 (https=) |
| CA (1) | CA3152931A1 (https=) |
| IL (1) | IL291509A (https=) |
| WO (1) | WO2021067291A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021127209A1 (en) * | 2019-12-17 | 2021-06-24 | Sigma-Aldrich Co. Llc | Genome editing in bacteroides |
| CN116004688A (zh) * | 2021-10-21 | 2023-04-25 | 中国科学院深圳先进技术研究院 | 肠道菌拟杆菌的基因编辑方法与应用 |
| US20250034579A1 (en) * | 2021-12-07 | 2025-01-30 | Cornell University | Methods and compositions for genetically modifying human gut microbes |
| KR20240172712A (ko) * | 2023-05-31 | 2024-12-10 | 한국생명공학연구원 | 아커만시아 뮤시니필라 tars를 발현 및 분비하도록 설계된 프로바이오틱스 및 이의 제조를 위한 벡터 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002306849A1 (en) * | 2001-03-21 | 2002-10-08 | Elitra Pharmaceuticals, Inc. | Identification of essential genes in microorganisms |
| JP5070051B2 (ja) * | 2004-06-07 | 2012-11-07 | クー バイオロジックス インク. | 癌を治療するための細菌組成物 |
| CA2682242A1 (en) * | 2007-03-28 | 2008-10-02 | Alimentary Health Limited | Probiotic bifidobacterium longum strain |
| US20110281762A1 (en) * | 2010-05-13 | 2011-11-17 | Sonnenburg Justin L | High throughput screening for anaerobic microorganisms |
| EP3241902B1 (en) * | 2012-05-25 | 2018-02-28 | The Regents of The University of California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| WO2015006294A2 (en) * | 2013-07-10 | 2015-01-15 | President And Fellows Of Harvard College | Orthogonal cas9 proteins for rna-guided gene regulation and editing |
| WO2015148680A1 (en) * | 2014-03-25 | 2015-10-01 | Ginkgo Bioworks, Inc. | Methods and genetic systems for cell engineering |
| US11408007B2 (en) * | 2014-09-26 | 2022-08-09 | Yale University | Compositions and methods for biocontainment of microorganisms |
| CN107667173A (zh) * | 2015-05-06 | 2018-02-06 | 斯尼普技术有限公司 | 改变微生物种群和改善微生物群 |
| EP3307306A4 (en) * | 2015-06-10 | 2019-04-24 | Massachusetts Institute of Technology | GENE EXPRESSION IN BACTEROIDES |
| JP6886142B2 (ja) * | 2017-01-04 | 2021-06-16 | 国立大学法人 新潟大学 | 腸内細菌叢改善剤及びその使用 |
-
2020
- 2020-09-29 US US17/037,141 patent/US20210095273A1/en not_active Abandoned
- 2020-09-29 JP JP2022520089A patent/JP2022549519A/ja active Pending
- 2020-09-29 CA CA3152931A patent/CA3152931A1/en active Pending
- 2020-09-29 KR KR1020227010378A patent/KR20220051259A/ko not_active Ceased
- 2020-09-29 BR BR112022005831A patent/BR112022005831A2/pt unknown
- 2020-09-29 AU AU2020357816A patent/AU2020357816A1/en not_active Abandoned
- 2020-09-29 WO PCT/US2020/053304 patent/WO2021067291A1/en not_active Ceased
- 2020-09-29 EP EP20792826.8A patent/EP4038185A1/en active Pending
- 2020-09-29 CN CN202080083063.1A patent/CN114929873A/zh active Pending
-
2022
- 2022-03-20 IL IL291509A patent/IL291509A/en unknown
-
2024
- 2024-05-29 JP JP2024087359A patent/JP2024116193A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR112022005831A2 (pt) | 2022-06-21 |
| WO2021067291A1 (en) | 2021-04-08 |
| US20210095273A1 (en) | 2021-04-01 |
| CA3152931A1 (en) | 2021-04-08 |
| EP4038185A1 (en) | 2022-08-10 |
| KR20220051259A (ko) | 2022-04-26 |
| JP2022549519A (ja) | 2022-11-25 |
| CN114929873A (zh) | 2022-08-19 |
| IL291509A (en) | 2022-05-01 |
| JP2024116193A (ja) | 2024-08-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dong et al. | Exploiting a conjugative CRISPR/Cas9 system to eliminate plasmid harbouring the mcr-1 gene from Escherichia coli | |
| US20210095273A1 (en) | Modulation of microbiota compositions using targeted nucleases | |
| Nayak et al. | Cas9-mediated genome editing in the methanogenic archaeon Methanosarcina acetivorans | |
| JP2021000092A (ja) | 細胞工学のための方法および遺伝システム | |
| CN108026536A (zh) | 使用crispr核酸筛选细菌、古细菌、藻类和酵母的方法 | |
| US20250354158A1 (en) | Cis conjugative plasmid system | |
| AU2003298291A1 (en) | Self-containing lactobacillus strain | |
| Chen et al. | Complete nucleotide sequence of plasmid pST-III from Lactobacillus plantarum ST-III | |
| JP2024125308A (ja) | バクテロイデスにおけるゲノム編集 | |
| Álvarez-Martín et al. | Improved cloning vectors for bifidobacteria, based on the Bifidobacterium catenulatum pBC1 replicon | |
| EP4229199A1 (en) | Targeted-antibacterial-plasmids combining conjugation and crispr /cas systems and uses thereof | |
| Steigedal et al. | The Acinetobacter sp. chnB promoter together with its cognate positive regulator ChnR is an attractive new candidate for metabolic engineering applications in bacteria | |
| JP6412865B2 (ja) | ビフィドバクテリウム・ブレーベ株特異的遺伝子 | |
| Shi et al. | Engineering and characterization of a symbiotic selection-marker-free vector-host system for therapeutic plasmid production | |
| Friess et al. | A CRISPRi gene regulation system for bifidobacteria | |
| CN1989255A (zh) | 降低细胞中的自发突变率 | |
| Xie et al. | Exploiting the Endogenous Type II‐A CRISPR‐Cas System for Functional Engineering of Probiotic Lacticaseibacillus rhamnosus GG | |
| Song et al. | Establishment of a CRISPR interference (CRISPRi) system in Limosilactobacillus reuteri AR673 | |
| El Bakkoury et al. | Bacteriocin peer selection for the production of antibiotic selection free biotherapeutic pDNA | |
| Fontebasso | Improving strategies to develop anti-Candida treatments based on the vaginal species L. gasseri: from molecular approaches to physiological analyses. | |
| WO2024096123A1 (ja) | 遺伝子が改変された微生物およびその生産方法 | |
| Disha et al. | Factors and Conditions That Impact Electroporation of Clostridioides difficile Strains | |
| Yang et al. | Genomic integration and expression of the Aggregatibacter actinomycetemcomitans catalase gene in Aggregatibacter aphrophilus | |
| Selle | Functional Genomic Studies of Lactic Acid Bacteria | |
| KR20160027582A (ko) | 자살벡터를 이용하여 다제내성 균주의 변이주를 제작하는 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |